1) The temperature dependence of the marked nonideality of concentrated hemoglobin solutions has been found to be negligible. This result is in accord with the representation of these solutions as non-interacting quasispherical particles and justifies the application of activity coefficients obtained at one temperature to characterize the thermodynamics and kinetics of sickle cell hemoglobin gelation over the whole temperature range for which experimental data exist (2-37 degrees C). 2) Based upon this model and applying the concentration dependence of the frictional coefficient of sedimentation to diffusion, the concentration dependence of the diffusion coefficient of hemoglobin solutions (0-35%) which is a combined hydrodynamic and thermodynamic property has successfully been accounted for 3). In order to provide a rational approach to the inhibition of the gelation of sickle cell hemoglobin a systematic study of the effects of ions and organic molecules upon the solubility of deoxyhemoglobin S (HbS) has been carried out. From these results and the current understanding of the microtubular structure of HbS fibers we have proposed a detailed stereochemical mechanism of the noncovalent inhibition of gelation of HbS which accounts for the effects of all inhibitors reported to date and successfully predicts the design of more effective inhibitors.